Alzheimer's disease, which is a brain disorder that destroys brain cells by a destructive accumulation of amyloid-beta protein and generally outbreaks with aging, is a serious disease resulting in speech impediment and recognition disorder. Alzheimer's disease proceeds in stages and gradually destroys memory, reasoning, judgment, language, and the ability to carry out even simple tasks. Eventually, loss of emotional control may cause degradation of human life. Currently, Alzheimer's disease cannot be completely cured, but drugs relieving symptoms are clinically applied. However, effects of these drugs on patients are limited. Around half of Alzheimer's disease patients fail to be cured from initial drug treatment. Even if the initial drug treatment is successful, only a slight alleviation of symptoms is experienced. Thus, there is a need to develop a novel treatment for satisfying medical demands, and the development of a treatment for Alzheimer's disease will have large economical and social effects. It is known that as Alzheimer's disease proceeds, the cerebral cortex and hippocampus are destroyed and cannot be restored, and thus there is no treatment therefor.
Research on Alzheimer's disease has been driven by a focus on two proteins, tau and amyloid precursor protein (APP) (Stuart M. and Mark P. M, Nature Medicine, 12(4), 392-393, 2006). Brains of affected individuals accumulate aberrant forms of both of these proteins. Tau becomes hyperphosphorylated and APP is cleaved by secretase to produce amyloid-beta (Aβ) protein which aggregates in the brain in plaque form. In general, the number of synapses is reduced and neurites are damaged in brain regions in which plaque is accumulated. This indicates that the amyloid-beta damages synapses and neurites (Mark P. M, Nature, 430, 631-639, 2004).
Research on pathogenetic mechanism has been actively conducted for the treatment of Alzheimer's disease. In particular, research on an inhibitor of beta-secretase and/or gamma-secretase producing amyloid-beta protein, a protease degrading accumulated amyloid-beta protein, and an inhibitor of acetylcholine esterase degrading acetylcholine have been intensively performed. Furthermore, research on a treatment for Alzheimer's disease using an inflammation inhibitor has been conducted since Alzheimer's disease is an aging-related chronic inflammatory disease.
The amount of amyloid-beta in the brain is determined by the balance between reactions for production and removal of the amyloid-beta. Accordingly, if the amyloid-beta removal is reduced, the amount of amyloid-beta is increased. Deficiency of neprilysin (NEP), which is an enzyme with activity for degrading amyloid-beta, results in accelerating extracellular accumulation of amyloid (Kanae Iijima-Ando, etc., J. Biol. Chem., 283(27), 19066-19076, 2008).
Abnormal neurites projected from a cell body of a neuron is related to neural diseases. Examples of the neural diseases are Alzheimer's disease, Parkinson's disease, depression, epilepsy, multiple sclerosis, and mania. In particular, epilepsy occurs due to death of neuron and gliosis of human hippocampus. Neurites are cleaved by the death of neuron. Multiple sclerosis is a chronic autoimmune disease occurring in the brain due to abnormalities of Nogo A, a neurite outgrowth inhibiting protein. Depression is a brain disorder caused by abnormalities of M6a, a neurite outgrowth-related protein. Alleviation of symptoms of mania has been reported in mice by activating a signal transduction pathway stimulating neurite outgrowth.
Mesenchymal stem cells (MSCs) are multipotent stem cells differentiating into mesodermal lineage cells such as osteocytes, chondrocytes, adipocytes, and myocytes or ectodermal lineage cells such as neurons. It has recently been reported that MSCs have a potential to differentiate into neuroglia in the brain, and thus attempts to differentiate MSCs into neurons have been made (Korean Patent Publication No. 10-2004-0016785, Feb. 25, 2004).
Among the MSCs, a bone marrow-derived MSC can be obtained from a patient. If the MSC is autologously transplanted, there is no immune rejection response, and thus can be clinically applied to patients. However, since bone marrow-derived MSC collection requires various stages of complicated medical treatments, bone marrow donation is time-consuming, psychologically and physically painful and expensive. However, since an umbilical cord blood-derived MSC is simply obtained from an umbilical cord, and the umbilical cord blood preservation industry is being actively developed, and donors are easily found due to the umbilical cord blood infrastructure, MSCs are easily obtained. Furthermore, MSCs obtained from allogeneic cord blood do not exhibit an immune response after transplantation, thereby exhibiting immunological stability.
All the cited references are incorporated herein by reference in their entireties.